Presynaptic calcium channel inhibition underlies CB1 cannabinoid receptor-mediated suppression of GABA release

Gergely G. Szabó, Nora Lenkey, N. Holderith, Tibor Andrási, Z. Nusser, Norbert Hájos

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

CB1 cannabinoid receptors (CB1) are located at axon terminals and effectively control synaptic communication and thereby circuit operation widespread in the CNS. Although it is partially uncovered how CB1 activation leads to the reduction of synaptic excitation, the mechanisms of the decrease of GABA release upon activation of these cannabinoid receptors remain elusive. To determine the mechanisms underlying the suppression of synaptic transmission by CB1 at GABAergic synapses, we recorded unitary IPSCs (uIPSCs) at cholecystokinin-expressing interneuron-pyramidal cell connections and imaged presynaptic [Ca2+] transients in mouse hippocampal slices. Our results reveal a power function with an exponent of 2.2 between the amplitude of uIPSCs and intrabouton [Ca2+]. Altering CB1 function by either increasing endocannabinoid production or removing its tonic activity allowed us to demonstrate that CB1 controls GABA release by inhibiting Ca2+ entry into presynaptic axon terminals via N-type (Cav2.2) Ca2+ channels. These results provide evidence for modulation of intrabouton Ca2+ influx into GABAergic axon terminals by CB1, leading to the effective suppression of synaptic inhibition.

Original languageEnglish
Pages (from-to)7958-7963
Number of pages6
JournalJournal of Neuroscience
Volume34
Issue number23
DOIs
Publication statusPublished - 2014

Fingerprint

Cannabinoid Receptor CB1
Presynaptic Terminals
Calcium Channels
gamma-Aminobutyric Acid
Cannabinoid Receptors
Endocannabinoids
Pyramidal Cells
Cholecystokinin
Interneurons
Synaptic Transmission
Synapses
Communication
Inhibition (Psychology)

Keywords

  • Endocannabinoid
  • GABAergic interneuron
  • Hippocampus
  • Mouse

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Presynaptic calcium channel inhibition underlies CB1 cannabinoid receptor-mediated suppression of GABA release. / Szabó, Gergely G.; Lenkey, Nora; Holderith, N.; Andrási, Tibor; Nusser, Z.; Hájos, Norbert.

In: Journal of Neuroscience, Vol. 34, No. 23, 2014, p. 7958-7963.

Research output: Contribution to journalArticle

Szabó, Gergely G. ; Lenkey, Nora ; Holderith, N. ; Andrási, Tibor ; Nusser, Z. ; Hájos, Norbert. / Presynaptic calcium channel inhibition underlies CB1 cannabinoid receptor-mediated suppression of GABA release. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 23. pp. 7958-7963.
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